The Est1 subunit of Saccharomyces cerevisiae telomerase makes multiple contributions to telomere length maintenance

Genetics. 2002 Nov;162(3):1101-15. doi: 10.1093/genetics/162.3.1101.

Abstract

The telomerase-associated Est1 protein of Saccharomyces cerevisiae mediates enzyme access by bridging the interaction between the catalytic core of telomerase and the telomere-binding protein Cdc13. In addition to recruiting telomerase, Est1 may act as a positive regulator of telomerase once the enzyme has been brought to the telomere, as previously suggested by the inability of a Cdc13-Est2 fusion protein to promote extensive telomere elongation in an est1-Delta strain. We report here three classes of mutant Est1 proteins that retain association with the telomerase enzyme but confer different in vivo consequences. Class 1 mutants display a telomere replication defect but are capable of promoting extensive telomere elongation in the presence of a Cdc13-Est2 fusion protein, consistent with a defect in telomerase recruitment. Class 2 mutants fail to elongate telomeres even in the presence of the Cdc13-Est2 fusion, which is the phenotype predicted for a defect in the proposed second regulatory function of EST1. A third class of mutants impairs an activity of Est1 that is potentially required for the Ku-mediated pathway of telomere length maintenance. The isolation of mutations that perturb separate functions of Est1 demonstrates that a telomerase holoenzyme subunit can contribute multiple regulatory roles to telomere length maintenance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amino Acids, Acidic
  • Amino Acids, Basic
  • Conserved Sequence
  • DNA Mutational Analysis
  • Gene Expression Regulation, Fungal
  • Mutagenesis, Site-Directed
  • Mutation, Missense
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Alignment
  • Telomerase / genetics*
  • Telomerase / metabolism*
  • Telomere / genetics*
  • Telomere-Binding Proteins / metabolism

Substances

  • Amino Acids, Acidic
  • Amino Acids, Basic
  • Cdc13 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Telomere-Binding Proteins
  • EST1 protein, S cerevisiae
  • Telomerase